The ribosome, the organelle essential for protein synthesis, obviously plays a key role in cell growth and its regulation. In bacteria, the number of ribosomes in a cell is directly proportional to the growth rate of the cells under various culture conditions (except under conditions of very slow growth). The average rate of protein synthesis per ribosome in rapidly and slowly growing cells is the same, but the presence of more ribosomes in rich media permits more protein to be made and thus accounts for an overall increase in growth rate. Our goal is to understand how bacteria regulate the production of ribosomes and their growth rate. Specifically, our recent effort has focused on the identification of genes for ribosomal proteins and rRNA, and studies of the regulation of the expression of these important genes. We have recently discovered that ribosomal protein synthesis and ribosome assembly are coupled such that when ribosomal protein synthesis exceeds the rate of ribosome biosynthesis certain key ribosomal proteins act as inhibitors that prevent the further translation of their own mRNA. This feedback regulation model can account for coordinate and balanced synthesis of all of the ribosomal protein components. We will continue to study detailed mechanisms involved in the translational feedback regulation of ribosomal protein synthesis. In addition, we will study possible transcriptional regulation of ribosomal protein gene expression that might be operating as an important regulatory mechanism under some other conditions, e.g., during stringent control. Finally, we will study both in vivo and in vitro transcriptional regulation of rRNA gene expression which is fundamental to our understandig global regulation of ribosome accumulation in growing cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035949-03
Application #
3289438
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1985-06-01
Project End
1988-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Nomura, Masayasu (2011) Journey of a molecular biologist. Annu Rev Biochem 80:16-40
Anderson, Susan J; Sikes, Martha L; Zhang, Yinfeng et al. (2011) The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. J Biol Chem 286:18816-24
Nomura, Masayasu (2009) Switching from prokaryotic molecular biology to eukaryotic molecular biology. J Biol Chem 284:9625-35
Hontz, Robert D; French, Sarah L; Oakes, Melanie L et al. (2008) Transcription of multiple yeast ribosomal DNA genes requires targeting of UAF to the promoter by Uaf30. Mol Cell Biol 28:6709-19
French, Sarah L; Osheim, Yvonne N; Schneider, David A et al. (2008) Visual analysis of the yeast 5S rRNA gene transcriptome: regulation and role of La protein. Mol Cell Biol 28:4576-87
Schneider, David A; Michel, Antje; Sikes, Martha L et al. (2007) Transcription elongation by RNA polymerase I is linked to efficient rRNA processing and ribosome assembly. Mol Cell 26:217-29
Oakes, Melanie L; Johzuka, Katsuki; Vu, Loan et al. (2006) Expression of rRNA genes and nucleolus formation at ectopic chromosomal sites in the yeast Saccharomyces cerevisiae. Mol Cell Biol 26:6223-38
Oakes, Melanie L; Siddiqi, Imran; French, Sarah L et al. (2006) Role of histone deacetylase Rpd3 in regulating rRNA gene transcription and nucleolar structure in yeast. Mol Cell Biol 26:3889-901
Schneider, D A; French, S L; Osheim, Y N et al. (2006) RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. Proc Natl Acad Sci U S A 103:12707-12
Schneider, David A; Nomura, Masayasu (2004) RNA polymerase I remains intact without subunit exchange through multiple rounds of transcription in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 101:15112-7

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